It is estimated that over half of men over age 50 and three quarters of men over age 70 experience benign prostatic hyperplasia (BPH). BPH is a condition characterized by a swelling of the prostate; the gland is responsible for secreting an alkaline fluid that is incorporated in seminal fluid. The prostate gland is located below the bladder and surrounds part of the urethra. While prostate enlargement is regarded as a normal part of aging, BPH progression can cause a number of lower urinary tract symptoms and related complications. As the prostate swells, the urethra becomes constricted and obstructs the bladder. This obstruction leads to many of the symptoms of BPH: painful urination, decreased flow, difficulty starting or stopping flow, nocturnal urination, incomplete voiding and others. Complications such as recurrent urinary tract infections, pyelonephritis, chronic and acute urinary retention, dilatation and hydronephrosis can also occur. In some cases, BPH has also been linked to chronic and acute renal failure.
There are two general approaches to addressing BPH: drug treatment and surgery. Currently available drug treatments include the use of alpha-blockers, hormonal therapeutics and herbal medicines. Alpha-blockers relax smooth muscle by selectively blocking alpha-1 adrenoreceptors in the bladder neck and prostate, thereby relieving some of the symptoms associated with BPH. This class includes drugs such as prasozin, doxazosin, indoramin, asfuzasin, terazosin and tamsulosin. Disadvantages of the alpha-blockers include frequency of dosing, side effects and cost. Hormonal therapeutics are anti-androgens that prevent certain hormonal changes involved with BPH. Finasteride (Proscar.RTM., Merck & Co., Inc.) is the leading drug of this class. It prevents the production of dihydrotestosterone (DHT), an androgen that accumulates within the prostate and causes the prostatic enlargement associated with BPH. Finasteride acts by specifically inhibiting steroid 5-alpha reductase, an enzyme responsible for converting testosterone into DHT. Although relatively free from side effects, finasteride is expensive and has a much slower onset of action than the alpha-blockers.
Herbal medicines are a popular alternative to synthetic drugs for treating BPH. These include phytosterols (e.g., beta-sitosterol), saw palmetto berry extracts, Pinus extracts, Picea extracts, Hypoxis extracts, Redix urticae extracts, pumpkin seed extracts (such as cubicin), pygeum, ginseng, cayenne (capsicum), goldenseal root and pollen extracts (such as cernilton).
Despite the existence of these therapeutic options, surgery remains the most effective method of treating BPH, particularly in cases of acute and chronic retention. Surgical methods include transurethral resection of the prostate, transurethral incision, thermotherapy, stents and ultrasound. However, the inherent dangers of surgery, the frequency of post-operative morbidity and the likelihood of needing repeat procedures make surgery an undesired option.
Accordingly, there is still a well-recognized and unmet need for new agents to treat benign prostatic hyperplasia.